Can trazodone (Trazodone hydrochloride) cause acquired QT (QT interval) prolongation?

From the Guidelines

Trazodone can cause acquired QT interval prolongation, particularly at higher doses or with prolonged treatment durations, as evidenced by case reports and studies 1.

Key Factors Influencing QT Prolongation Risk

• Dose: Higher doses, typically exceeding 200-300 mg per day, increase the risk of QT interval prolongation 1.
• Treatment Duration: Prolonged treatment durations may also contribute to the risk of QT prolongation.
• Concomitant Medications: The use of other QT-prolonging medications concurrently with trazodone can potentiate this effect.

Recommendations for Safe Use

• Therapeutic Doses: At typical therapeutic doses ranging from 50-150 mg per day, the risk of QT prolongation is considered low, but careful monitoring is still advised, especially in patients with pre-existing cardiovascular conditions or those taking concomitant medications that may increase this risk 1.
• ECG Monitoring: Regular monitoring of electrocardiogram (ECG) results is recommended to promptly identify any QT interval prolongation.
• Risk-Benefit Analysis: The decision to use trazodone should be based on a thorough risk-benefit analysis, considering the potential therapeutic benefits against the risk of QT prolongation and torsades de pointes (TdP) 1.

From the FDA Drug Label

Trazodone Hydrochloride Tablets prolongs the QT/QTc interval. The use of Trazodone Hydrochloride Tablets should be avoided in patients with known QT prolongation or in combination with other drugs that are inhibitors of CYP3A4 (e.g., itraconazole, clarithromycin, voriconazole), or known to prolong QT interval including Class 1A antiarrhythmics (e.g., quinidine, procainamide) or Class 3 antiarrhythmics (e.g., amiodarone, sotalol), certain antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine), and certain antibiotics (e.g., gatifloxacin). Concomitant administration of drugs may increase the risk of cardiac arrhythmia [see DRUG INTERACTIONS (7.1)]. QTIntervalProlongation ClinicalImpact:Concomitant use of drugs that prolong the QT interval may add to the QT effects of Trazodone hydrochloride tablets and increase the risk of cardiac arrhythmia. The most severe reactions reported to have occurred with overdose of Trazodone Hydrochloride Tablets alone have been priapism, respiratory arrest, seizures, and ECG changes, including QT prolongation.

Trazodone (Trazodone hydrochloride) can cause acquired QT (QT interval) prolongation. This is supported by the drug label, which explicitly states that Trazodone Hydrochloride Tablets prolong the QT/QTc interval and should be avoided in patients with known QT prolongation or in combination with other drugs that prolong the QT interval 2, 2, 2.

From the Research

Trazodone and QT Interval Prolongation

• Trazodone hydrochloride has been studied for its effect on the QT interval, with a study published in 2020 3 finding a modest, dose-dependent effect on cardiac repolarization.
• The study found that trazodone had no QTc prolongation observed with the 20-mg dose, but an effect exceeding the values set in E14 guideline with the 60- and 140-mg doses.
• Another study published in 2018 4 reviewed the evidence on the risk of QTc prolongation associated with antidepressant use in older adults, but did not specifically focus on trazodone.
• A study from 2005 5 compared the effects of antipsychotic monotherapy versus polytherapy (including antidepressants) on QT interval prolongation, but did not specifically examine trazodone.
• An older review from 1994 6 discussed the pharmacology and therapeutic use of trazodone, but did not mention QT interval prolongation as a specific concern.
• A review from 2010 7 discussed drug- and non-drug-associated QT interval prolongation, but did not specifically focus on trazodone.

Key Findings

• The 2020 study 3 found that trazodone had a dose-dependent effect on QT interval prolongation, with higher doses (60- and 140-mg) exceeding the values set in E14 guideline.
• The study suggested that the effect on cardiac repolarization is unlikely to represent a clinical risk for ventricular proarrhythmia, but caution should be used with concomitant use of other medications that prolong QT or increase trazodone exposure.
• Other studies 4, 5, 6, 7 did not provide direct evidence on the relationship between trazodone and QT interval prolongation.